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18 1910 


On  the  Theory  of  Indicators  and  the 

Reactions  of  Phthaleins  and 

Their  Salts 


DISSERTATION 


SUBMITTED  TO   THE    BOARD  OF    UNIVERSITY   STUDIES  OF 
THE  JOHNS  HOPKINS  UNIVERSITY   IN   CONFORMITY 
WITH    THE    REQUIREMENTS   FOR    THE    DE- 
GREE OF  DOCTOR  OF  PHILOSOPHY 


(  I 

EDGAR  APPLE  SLAGLE 


1909 


EASTON,  PA.  : 

ESCHENBACH  PRINTING  COMPANY. 
1909 


On  the  Theory  of  Indicators  and  the 

Reactions  of  Phthaleins  and 

Their  Salts 


DISSERTATION 


SUBMITTED  TO  THE   BOARD  OF   UNIVERSITY  STUDIES  OF 
THE  JOHNS  HOPKINS  UNIVERSITY  IN   CONFORMITY 
WITH   THE   REQUIREMENTS  FOR    THE   DE- 
GREE OF  DOCTOR  OF  PHILOSOPHY 


BY 

EDGAR  APPLE  SLAGLE 

BALTIMORE 

1909 


'EASTON,  PA.  : 

ESCHENBACH  PRINTING    COMPANY, 
1909 


CONTENTS. 


Acknowledgment 4 

Part    I.     Theoretical 5 

Part  II.     Experimental 20 

Fluorescein 20 

Phenolphthalein 24 

/>-Oxydiphenylphthalid 27 

The  Dilatometer 29 

A  New  Dilatometer 35 

Biographical 38 


228295 


ACKNOWLEDGMENT. 

The  author  takes  pleasure  in  expressing  his  gratitude  to 
President  Remsen,  Professor  Morse,  Professor  Jones,  Professor 
Ames,  Professor  Renouf,  Associate  Professor  Acree  and  Dr. 
Gilpin,  for  instruction  in  the  class  room  and  laboratory. 

Especially  does  he  wish  to  express  his  sincere  gratitude  and 
thanks  to  Associate  Professor  Acree,  under  whose  personal 
direction  this  investigation  has  been  pursued. 


On  the  Theory  of  Indicators  and 

the  Reactions  of  Phthaleins 

and  Their  5alts 


The  rapid  advance  in  our  knowledge  of  the  constitution 
and  reactions  of  colored  compounds  of  the  aromatic  series 
has  made  it  clear  that  we  must  seek  the  cause  of  the  manifes- 
tation of  color  in  some  deep-seated  change  in  the  molecule 
itself.  The  view  formerly  held  that  the  color  of  these  par- 
ticular benzene  derivatives  is  a  function  only  of  the  increase 
in  the  molecular  weight,  or  depends  upon  the  introduction 
of  certain  elements  or  groups  which  tend  to  produce  color, 
has  long  been  abandoned. 

The  first  important  attempt  to  formulate  a  theory  of  color 
is  seen  in  the  hypothesis  of  O.  N.  Witt,1  brought  out  in  1876, 
in  which  he  assumed  in  all  colored  compounds  the  presence 
of  certain  specific  groups  (nitro,  azo,  cyan,  etc.)  which  were 
thought  to  be  responsible  for  the  color.  Witt  called  these 
groups  chromophores.  He  recognized  in  some  cases  the  ad- 
ditional influence  of  certain  salt-forming  groups  (hydroxyl, 
amino,  etc.)  which  intensify  the  color  of  the  chromophore 

i  Ber.  d.  chem.  Ges.,  9,  522. 


and  give  to  the  compound  the  properties  necessary  in  mak- 
ing the  dye  practically  useful.  These  latter  groups  were 
called  auxochromes  . 

The  quinone  theory  was  first  advanced  by  K.  and  O.  Fischer 
to  explain  the  colors  of  the  dyestuffs  of  the  rosaniline  series 
and  is  really  an  extension  of  Witt's,  which  gives  a  more  defi- 
nite meaning  to  the  term  chromophore. 

In  1889  Nietzki1  extended  the  quinone  theory,  using,  how- 
ever, the  modern  formula  of  quinone,  to  the  indamine  and 
azine  series.  This  conception  was  shortly  after  extended  by 
Armstrong  to  include  all  colored  compounds  of  the  aromatic 
group. 

In  1893  Friedlander2  assigned  a  corresponding  quinone 
structure  to  phenolphthalein  salts.  He  accepted  Baeyer's 
formula  for  phenolphthalein  in  the  free  condition, 


/64\ 

(C6H4OH)2C<          )>CO, 
^   O  / 

but  assumed  that  an  intramolecular  change  takes  place  in  the 
molecule  in  the  presence  of  alkalies  which  results  in  the  forma- 
tion of  the  colored  quinone  salt, 

NaOOCC6H4C(  :  C6H4  :  O)  (C6H4ONa)  , 
which  he  assumed  to  be  analogous  to  the  salts  of  aurin, 

(NaOC6H4)2C  :  C6H4  :  O, 

and  of  rosolic  acid,  / 

(NaOC6H4)(0  :C6H4  :  )C[C6H3(CH3)ONa]. 

As  a  proof  of  the  existence  of  the  quinone  structure  in  the 
salt 

(KOOCC6H4)C(  :C6H4  :0)(C6H4OK), 

he  prepared  an  oxime  by  treating  an  alkaline  solution  of  phenol- 
phthalein with  hydroxylamine.  Friedlander  also  suggested 
that  phenolphthalein  is  a  dibasic  acid  and  that  the  salts  are 
dibasic  salts,  but  it  remained  for  Meyer  and  Spengler8  to  prove 

1  Organische  Farbstoffe,  1st  Edition,  p.  2. 

2  Ber.  d.  chem.  Ges.,  26,  172. 
*  Ibid.,  38,  1318. 


this  by  isolating  and  analyzing  the  salt  C20H12O4Na2.  At 
about  the  same  time  Bernsthen1  came  to  similar  conclusions 
in  his  researches  on  rhodamine  6  G  and  suggested  that  fluor- 
escein  exists  in  the  free  condition  as  the  lactone  compound 
but  has  the  quinone  structure  in  its  salts. 

A  few  years  ago  another  conception  of  the  cause  of  color 
was  advanced  by  Baeyer2  and  called  by  him  halochromy. 
He  assumed  the  existence,  in  colored  bodies  of  the  triphenyl- 
methane  series,  of  a  peculiar  form  of  valence  represented  by 
a  wavy  bond,  C-\_x~ _C1,  which  Baeyer  and  Villiger  called  the 
carbonium  valence.  In  this  condition  carbon  was  assumed 
to  act  as  a  strongly  basic  element  which  brings  about  the 
manifestation  of  color.  This  theory  has  recently  been  given 
up  by  Baeyer. 

In  1890  Ostwald3  proposed  an  explanation  of  color  changes 
based  on  the  theory  of  electrolytic  dissociation.  He  assumed 
phenolphthalein  to  be  an  extremely  weak  acid  and  conse- 
quently but  little  dissociated;  on  the  addition  of  an  alkali 
a  salt  is  formed  which  is  largely  dissociated,  and  the  red  color 
was  thought  to  be  due  to  the  anion.  The  work  on  the  physical 
constants  of  phenolphthalein  has  shown  that  a  close  quanti- 
tative relationship  exists  between  Ostwald's  theory  and 
color  change,  yet  many  facts  make  it  evident  that  this  theory 
is  in  itself  not  able  to  account  for  all  of  the  known  phenomena. 
While  it  is  true  that  the  negative  ions  are  colored,  the  change 
in  color  is  due  to  a  change  in  constitution  of  the  compound, 
the  ions  having  a  structure  different  from  that  of  the  mother 
substance. 

In  1903  Stieglitz4  published  a  valuable  article  on  the  theory 
of  indicators.  By  the  use  of  (a)  the  evidence  on  the  quinone 
theory  furnished  by  Friedlander  and  Nietzki,  (b)  Hantzsch's 
ideas  and  equations  concerning  pseudoacids,  and  (c)  Ost- 
wald's conception  of  the  quantitative  relationships  in  the 
indicator  work,  Stieglitz  came  to  the  conclusion,  in  con- 

i  Chem.  Ztg.,  1892,  1956. 
3  Ber.  d.  chem.  Ges.,  38,  570,  1156. 

8  Lehrbuch  der  allgemeinen  Chemie,  1891,  p.  462;  Scientific  Foundations  of 
Analytical  Chemistry,  1890.  ;. 

*  J.  Am.  Chem.  Soc.,  25,  1112. 


8 

sidering  phenolphthalein,  that  (p.  1115)  "its  red  salts  are 
the  salts  of  a  carboxylic  acid,  not  a  phenol,  and  have  the  con- 
stitution 

(MOOCC6H4)(HOC6H4)C  :  C6H4  :  O. 

The  strongly  chromophoric  quinoid  complex  (  :  C6f/4  : 0)  gives 
us  an  explanation  of  the  production  of  intense  color,  which  is 
entirely  adequate  in  view  of  the  laws  governing  color  in  or- 
ganic compounds."  After  developing  the  equation 

CQ  X  CH  =  K"  X  CLH 

for  the  affinity  constant  of  the  phenolphthalein  he  stated 
(p.  1122)  that  "its  tendency  to  produce  the  red  color  (the  red 
salt)1  is  measured  by  the  same  constant  K"."  Hantzsch2 
points  out  that  he  too  had  proposed  this  theory. 

In  1905  Meyer  and  Spengler3  published  a  very  important 
article  in  which  they  showed  that  the  colored  salts  of  phenol- 
phthalein are  dibasic  salts,  but  they  discarded  the  quinone 
hypothesis  and  accepted  Baeyer's  theory  of  halochromy. 

In  May,  1906,  Acree  and  Brunei4  began  an  investigation 
on  indicators  as  a  part  of  their  work  on  tautomerism.  It 
was  seen  by  them  that  previous  theories  did  not  account 
fully  for  either  the  color  phenomena  or  the  alkylation  reac- 
tibns  of  aurin,  phenolphthalein,  fluorescein,  etc.,  and  they 
began  work  on  these  substances  from  the  point  of  view  that 
the  tautomeric  mono-  and  dibasic  phenol  and  carboxyl  salts 
are  concerned  in  the  alkylation  reactions  and  in  the  color 
phenomena.  It  was  seen,  for  instance,  as  had  already  been 
surmised  by.  Friedlander,5  that  the  chief  source  of  color  in  the 
salts  of  aurin,  phenolphthalein,  etc.,  is  not  the  quinone  group 
assumed  by  practically  all  of  the  other  workers,  but  a  quinone- 
phenolate  group, 
— C(  :C6H4  :0)(C6H4ONa); 

(KOOCC6H4)C(  :  C6H4  :  O)(C6H4OK) ; 

(KOC6H4)C(  :  C6H4  :  O)(C6H4OK). 

1  All  the  italics  and  words  in  parentheses  are  mine  for  emphasis. 

2  Ber.  d.  chem.  Ges.,  39,  1090.     Rohland:  Ibid.,  40,  2172. 
3 /&«*.,  38,  1318. 

*  Amer.  Chem.  J.,  37,  71.     See  also  Ibid.,  27,  118;  31,  185;  32,  606;  37,  361;  38» 
1;  39,  124,  226;     Ber.  d.  chem.  Ges.,  35,  553;  36,  3139;  37,  184,  618;  41,  3199., 
5  Ber.  d.  chem.  Ges.,  26,  172. 


It  was  clear  that  the  four  possible  mono-  and  dibasic  salts, 
A,  B,  C  and  D,  must  be  represented  as  follows: 

(KOOCC,H4)C(  :  CGH4  :  O)(C6H4OH) 
A.     Faintly  colored. 

<C6li4K          yCgJn^OH 
n    , 


O    /         XC6H4OK 
B.     Colorless. 

(KOOCC()H4)C(  :  C6H4  :  O)(C6H4OK) 
C.     Deeply  colored. 

/C6H4OK 


x   O  /        XC6H4OK 
D.  Colorless. 

The  compound  A,  assumed  by  others  to  be  the  colored 
salt  of  phenolphthalein,  can  give  only  faintly  colored  solu- 
tions, the  carboxylphenoldibasic  salt,  C,  being  the  salt  really 
chiefly  responsible  for  the  color  changes.  B  and  D  were 
thought  to  be  colorless,  as  are  the  corresponding  esters.  This 
was  perfectly  apparent  from  the  work  of  Nietzki  and  Burck- 
hardt  and  Schroeter1  on  the  fluorescein  and  phenolphthalein 
derivatives,  and  from  the  long  known  work  on  rosolic  acid 
and  aurin,  which  was  pointed  out  by  Friedlander;  but  the 
significance  of  these  facts  was  unfortunately  entirely  over- 
looked by  the  other  workers  who  referred  to  these  articles, 
a  fact  which  shows  that  even  the  most  brilliant  human  minds 
are  very  imperfect  instruments  for  aiding  us  to  interpret 
nature's  phenomena.  The  faintly  colored  carboxyl  ester  of 
tetrabromphenolphthalein,  which  is  already  a  quinone, 

(C2H5OOCC6H4)C(  :C6H2Br2  : 0)(C6H2Br2OH), 
forms  a  deeply  colored  blue  potassium  or  silver  salt, 
(ROOCC6H4)C(  :C6H2Br2  :  O)(C6H2Br2OK). 

On  the  other  hand,  the  isomeric  phenol  ester,  which  accord- 
ing to  the  quinone  theory  should  yield  deeply  colored  salts, 
gives  practically  colorless  salts, 

»  Ber.  d.  chera.  Ges.,  28,  48;  SO,  178. 


(KOOCC6H4)C(  :C6H2Br2  :  O)(C6H2Br2OC2H5) 
Faintly  colored. 


OC<  V 

\   O   /       \C6H2Br2OC2H5 
Colorless. 

because  no  quinonephenolate  group  can  be  formed.  Espe- 
cially, though,  was  this  point  made  clear  by  the  properties  of 
aurin,  (HOC6H4)2C(  :  C6H4  : 0).  This  compound  has  al- 
ready a  quinone  group,  and  yet  when  alkali  is  added  to  an 
aqueous  solution  of  the  substance  there  is  formed  an  intensely 
colored  salt, 

(HOC6H4)(KOC6H4)C(  :  C6H4  :  O)     or     (KOC6H4)2C  :  C6H4  :  O. 

These  reactions  were  sufficient  to  show  that  the  quinone 
theory  alone  can  not  account  for  the  color  phenomena.  This 
view  has  been  recently  confirmed  more  fully  by  the  fact  ob- 
served by  Green  and  King1  that  the  faintly  colored  carboxyl 
ethyl  ester  of  phenolphthalein,  itself  a  quinone  derivative, 

(C2H5OOCC6H4)C(  :C6H4  :0)(C6H4OH), 
yields  the  intensely  colored  quinonephenolate  salt, 

(C2H5OOCC6H4)C(  :C6H4  :  O)(C6H4OK), 

whereas  the  isomeric  phenol  ethyl  ester  of  phenolphthalein, 
which  can  form  a  quinone,  but  not  a  quinonephenolate,  yields 
a  colorless  salt : 


(KOOCC6H4)C(  :  C6H4  :  O)(C6H4OR) 
Faintly  colored. 


OC/ 


O  /  '\C,H4OK 
Colorless. 


The  evidence  is  just  as  strong  that  both  phenol  and  car- 
boxyl salts  must  be  concerned  in  the  alkylation  reactions. 
Nietzki  and  Schroeter  found  that  their  "Fluorescein  Kalium" 
and  ethyl  bromide  gave  the  isomeric  colorless  phenol  and  col- 

1  Ber.  d.  chem.  Ges.,  40,  3724. 


ored  carboxyl  monoethyl  esters,  and  the  isomeric  colorless 
diphenol  die  thy  1  ester  and  colored  carboxylphenol  die  thy  1 
ester : 

/CeH4\       xC6H3(OC2H5)v  ^CeH3 : 0 

OC<  >C<  >0  C2H5OOCC6H4.Cf   >O 

\  O  '     XC6H3(OH)      /  N:6H3OH 

Colorless.  Colored. 

/C6H3(OC2H5) 
QC/  ^/ 


O  / 

Colorless. 

C2H5OOCC6H4.C/  >0 

\C6H3(OC2H5) 
Colored. 

These  esters  seemed  from  the  description  given  to  be  stable 
compounds  which  did  not  rearrange,  and  from  Acree's  theory 
of  tautomeric  compounds  it  seemed  hardly  likely  that  they 
were  formed  from  tautomeric  monobasic  salts,  but  altogether 
probable  that  they  were  obtained  from  tautomeric  dibasic 
fluorescein  salts.  Likewise  alkylation  experiments  by  Haller 
and  Guyot1  and  by  Herzig  and  Meyer2  with  phenolphthalein 
salts  yielded  85  to  90  per  cent  of  the  colorless  lactone  dimethyl 
ester,  whereas  Orndorff3  found  that  gallein  yields  both  qui- 
none  and  lactone  esters. 

Both  the  color  phenomena,  then,  and  the  alkylation  reac- 
tions pointed  to  the  presence  and  reactions  of  tautomeric 
dibasic  salts : 

(NaOOCCcH4)C( :  C6H4 : 0)  (C8H4ONa)   ^± 
A.  Colored. 

C  TT 
(NaOC6H4)2C/ 

\   O 
B.  Colorless. 

(NaOC,H4)2C-C8H4 

C8H5N— GO 
C.  Colorless. 

»  Compt.  Rend..  120,  296. 

8  Ber.  d.  chem.  Ges.,  28,  3259. 

a  Am.  Chem.  J.,  31,  97. 


12 

Acree  and  Brunei  believed  that  A  is  intensely  colored,  but 
that  salts  analogous  to  B  are  colorless,  just  as  the  correspond- 
ing salts  of  the  anilides,1  C,  are  without  color.  But  they 
thought  that  by  "  Fluorescein  Kalium"  Nietzki  and  Schroeter 
perhaps  meant  the  wonopotassium  salt,  and  if  this  had  been 
true  it  would  have  been  very  unfortunate  for  their  theory. 
They  accordingly  ordered  some  ''Fluorescein  Kalium"  from 
Hoeschst  and  Company  and  the  analysis  proved  that  it 
contained  more  than  3  atoms  of  potassium  to  one  molecular 
quantity  of  the  salt.  There  was  evidently,  therefore,  justifica- 
tion for  a  continuance  of  the  problem  from  their  point  of  view 
of  tautomeric  salts,  but  the  work  was  given  up  on  account 
of  the  departure  of  Dr.  Brunei  from  this  laboratory. 

In  the  meantime,  other  work  was  appearing  which  had  a 
very  direct  bearing  on  this  problem.  From  a  large  num- 
ber of  investigations  it  appeared  probable  that  we  might 
have  not  only  the  quinoid  and  lactoid  dibasic  salts  concerned 
in  the  colors,  but  also  still  another  tautomeric  salt,  an  intra- 
molecular condensation  product  of  the  phenol  salt  with  the 
carbonyl  of  the  quinone  group,  which  indeed  seemed  to  be 
the  chief  source  of  color  in  such  compounds: 

6H4:0 
ONa 


OC/       4\C(C«H4ONa2)  ^±  (NaOOCC6H4)C/ 
X  O  /  XC6H4 

I.  II. 


, 
(NaOOC.C6H4)C<    >O 


III. 

In  work  begun  in  1902,  Acree2  obtained  evidence  that  the 
i-phenyl-3-oxy-4-methyl-5-thiourazole  and  its  salts  could 
exist  not  only  in  the  two  tautomeric  forms,  I',  and  II'.,  ordi- 
narily assumed,  but  also  in  still  another  intramolecular  form, 
III'.,  analogous  to  III.: 

1  Meyer  and  Spengler:  Ber.  d.  chem.  Ges.,  36,  2949. 

2  Am.  Chem.  J.,  31,  187;  32,  606.      Nirdlinger:   Dissertation,  Johns  Hopkins  Uni- 
versity, 1909. 


13 

C6H5N— NNa  C6H5N— N  C6H5N— N 

II  I      II  I       II 

S:C     CO        ;z±        S:C     CONa  ;z±     NaSC      C— O 


N— CH,  NCH, 


NCR 


V.        .  II'.  III'. 

Busch  and  Opfermann1  later  actually  isolated  the  corre- 
sponding i,4-diphenyl-5-thiourazole  acids,  and  Busch  and  Rein- 
hardt2  showed  that  the  salts  can  exist.  Acree  and  Nird- 
linger  have  now  made  these  tautomeric  salts  and  actually 
proved  quantitatively  that  one  of  them  has  the  properties 
expected  of  a  compound  having  the  structure  III'.  Although 
these  salts  are  not  visibly  colored  yet  they  will  without  doubt 
be  found  to  have  different  colors  outside  the  visible  spectrum, 
as  do  many  other  such  compounds  (Baly,  Hardley,  Keyser, 
etc.).  The  actual  isolation  of  III',  proves  the  possible  ex- 
istence of  the  analogous  substance  III.,  and  as  long  ago  as 
I9043  it  was  pointed  out  that  such  intramolecular  salts  must 
be  considered  in  addition  to  the  ordinary  forms. 

Hantzsch,4  in  working  on  this  problem  of  the  cause  of 
color  in  salts,  had  to  assume  that  both  forms  of  the 
tautomeric  acids  are  ionized,  and  consequently  had  to 
give  up  his  former  idea  that  a  tautomeric  acid  exists  in  two 
forms,  one  of  which,  the  pseudoacid,  is  not  ionized,  while 
the  other,  the  "echt"  acid,  is  dissociated.  This  led  him 
then  to  assume  the  presence  of  two  salts  in  equilibrium, 
instead  of  the  one  salt,  that  of  the  "echt"  acid.  But  a  new 
idea  advanced  by  him  was  that  there  were  not  only  two 
tautomeric  salts  of  nitrophenol,  for  instance,  but  also  an- 
other intramolecular  salt,  III".,  analogous  to  III.,  with  a 
different  color  and  different  properties: 

1  Ber.  d.  chem.  Ges.,  37,  2333. 

2  Reinhardt:  Dissertation,  Erlangen,  1906. 

3  Amer.  Chem.  J.,  31,  187;  32,  606,  foot-note. 

4  Ber.  d.  chem.  Ges..  39,  1084;  40,  333. 


In  another  case  Hantzsch1  assumed  the  presence  of  such 
an  intramolecular  salt,  analogous  to  III.  He  found  that 
oxybenzaldehydes  and  oxybenzophenones  yield  different  col- 
ored salts  to  which  he  gave  the  formulas 


C(OK)C6H5 
O 


K 


(OK)C6H5 


The  chief  reason,  however,  for  believing  that  an  intra- 
molecular salt,  III.,  is  probably  the  chief  source  of  color  in 
the  phenolphthalein  series  came  from  work  by  Jackson2  and 
his  co workers,  by  Wichelhaus3  and  by  Posner.4  Jackson 
and  Oenslager5  and  Clarke,6  and  also  Wichelhaus,  showed 

1  Ber.  d.  chem.  Ges.,  39,  1084,  3080;  40,  335,  footnote,  etc. 

2  Their  articles  did  not  bear  especially  on  indicators. 

3  Ber.  d.  chem.  Ges.,  5,  849. 

4  Ann.  Chem.  (Liebig),  336,  85. 
6  Amer.  Chem.  J.,  18,  1. 

.,  34,  441. 


15 

that  when  a  quinone  adds  sodium  phenolate  or  sodium 
/?-naphtholate,  or  dime  thy  laniline,  the  intensely  colored 
double  salts, 

C6H4(ONa)2(OC6H5)2,  C6H4(ONa)2(/?-OC10H7)2, 

C6Br402.C6H5N(CH3)2,  C6C14O2.C6H5N(CH3)2, 

are  formed  in  nonaqueous  solvents.  Posner  ascribed  to 
these  compounds  different  constitutions,  but  that  question 
does  not  affect  the  theory.  It  was  therefore  a  question  to  be 
decided  by  experiment  whether  the  quinone  group  and 
the  sodium  phenol  group  of  II.  might  not  also  combine  to 
form  a  deeply  colored  salt,  III.,  even  in  aqueous  solutions. 
But  it  was  clear  that  the  experiments  would  actually  have 
to  be  done  in  aqueous  solutions,  in  which  the  color  changes 
of  phenolphthalein  manifest  themselves,  especially  as  Jackson 
found  the  quinonephenolate  addition  products  to  be  decom- 
posed by  water.1 

In  a  similar  way  it  is  clear  that  the  phenol  ester  salt  B, 
p.  126,  can  not  be  deeply  colored.  Since  the  phenol  esters  do 
not  unite  with  quinones  at  all,  the  color  of  B  is  simply  that 
of  the  quinone  group. 

If  the  theory  of  tautomeric  salts  is  to  explain  the  alkyla- 
tion  reactions  and  the  color  changes  of  phenolphthalein, 
etc.,  correctly,  three  things  must  be  proved  quantitatively, 
and  to  this  part  of  the  problem  I  have  now  devoted  my- 
self. 

I.  It  must  be  proved  by  experiment  that  fluorescein 
forms  the  tautomeric  dibasic  salts,  each  of  which  yields,  to 
some  extent,  its  corresponding  ester  in  independent  side  re- 
actions, no  ester  being  formed  entirely  by  a  rearrangement 
of  another  ester. 

I  have  now  been  able  to  do  this  in  a  clear-cut  way, 
as  is  brought  out  fully  in  the  experimental  portion.  The 
phenol  ethyl  ester  of  fluorescein,  for  instance,  forms  a  mono- 
sodium  salt  which  is  colored  and  which  exists  in  the  two 
forms  in  equilibrium  with  each  other: 

1  Jackson  and  Oenslager:  Amer.  Chem.  J.,  18*  16,  20. 


16 

t O r  /C6H4v 

(C2H5OC6H3)(NaOC6H3)C<(          >CO  ^ 

Vo  / 

A.    Colorless. 

r— O— i 
(C2H5OC6H3)  (O :  C6H3 :  )C(CeH4COONa) , 

B.  Colored 
and  with  their  hydrated  forms, 


(C2H5OC^H3)  (NaOC6H3)C(OH)  (C6H4COOH) 
Colorless. 

(C2H5OC6H3)  (HOC6H3)C(OH)  (C6H4COONa), 
Colorless. 

and  perhaps  with  the  intermolecular  salts. 

That  there  is  not  simply  one  salt,  B,  is  proved  by  the  fact 
that  this  sodium  salt  and  ethyl  iodide  yield  two  diethyl  esters, 
the  colored  quinone  ester  corresponding  to  B  and  the  colorless 
diphenol  ester  corresponding  to  A.  These  esters  do  not  re- 
arrange into  each  other  under  the  conditions  of  the  experi- 
ment and  hence  at  least  two  tautomeric  salts  must  be  pres- 
ent. 

This  theory  of  tautomeric  salts  accounts  very  nicely  also  for 
the  lack  of  color  in  some  of  these  salts.  Such  substances  as 
^-oxydiphenylphthalid,1  the  phenol  ethyl  ester  of  phenol- 
phthalein,2  and  the  corresponding  phenol  ester  of  tetrabrom- 
phenolphthalein,3  dissolve  in  alkalies  without  color.  Since 
each  of  these  compounds  yields  only  the  corresponding  lac- 
tone  ester  I  believe  that  the  salts  have  to  some  extent  the 
lactoid  form, 

/&£l*\     /Qft  xCftH4v       /C6H4OCHS 

OC<  >C<  and  OC<  >C< 

x   O  >      xC6H4ONa  \   O  /    xC6H4ONa 

This  may  be  in  equilibrium  with  the  hydrated  form, 
(CH3OC6H4)  (HOC6H4)C(OH)  (C6H4COONa) , 

1  Baeyer:  Ann.  Chem.  (Liebig),  354,  171. 

2  Ber.  d.  chem.  Ges.,  40,  3728. 

3  Ibid.,  30,  177. 


17 

which  Green  and  King1  assumed  to  be  the  structure  of  all 
these  colorless  salts.  But  I  do  not  think  that  this  point  of 
view  of  Green  and  King  accounts  for  the  formation  of  nearly 
quantitative  yields  of  the  phenol  dimethyl  ester  from  methyl 
iodide  and  the  sodium  salts  of  phenolphthalein  and  hydro- 
quinonephthalein,  of  the  phenyl  methyl  ester  of  dibrom-/?- 
oxydiphenylphthalid  from  the  sodium  salt  and  methyl  iodide, 
or  for  the  formation  of  both  isomeric  esters  of  fluorescein  ob- 
tained by  me :  my  theory  does  account  for  these  facts.  Since 
Green  and  King  assume  the  presence  of  a  hydrated  carboxyl 
salt  we  should  certainly  expect  to  obtain  some  carboxyl  ester 
if  their  theory  is  correct;  but  no  carboxyl  ester  is  formed, 
apparently,  from  the  colorless  salts  mentioned  above.  It  is 
unfortunate  that  no  one  has  isolated  these  colorless  salts 
and  shown  by  analysis  whether  they  are  hydrated  and  be- 
come colored  when  dehydrated,  or  whether  the  carboxyl 
esters  rearrange  into  phenol  esters.  That  these  salts  may 
actually  exist  in  the  lactoid  form  is  proven,  it  seems  to  me, 
by  the  fact  that  Meyer  and  Spengler2  actually  made  the  col- 
orless lactoid  salts  of  the  anilides  of  phenolphthalein  and 
hydroquinonephthalein.  This  is  a  very  important  phase  of 
my  work  and  it  will  be  continued  in  this  laboratory  from 
several  points  of  view. 

II.  It  must  be  proved  that  these  quinonephenolate  double 
salts  of  Jackson  and  Oenslager  and  of  Wichelhaus  and  the 
quiaminones  of  Jackson  and  Clarke  are  formed  in  aqueous 
solutions.  If  these  were  decomposed  completely  into  their 
constituents  in  water,  it  is  evident  that  these  substances 
could  not  be  concerned  in  the  color  changes  of  indicators 
and  dyestufTs  as  they  are  ordinarily  used.  I3  have  fortu- 
nately been  able  to  prove  that  deeply  colored  compounds 
are  formed  by  the  union  of  benzoquinone  or  anthraquinone 
with  salts  of  o-cresol,  />-cresol,  phenol,  hydroquinone,  pyro- 
gallol  and  resorcinol,  the  colors  of  which  disappear  when 
acids  are  added.  In  fact  such  mixtures  serve  as  very  good 
indicators.  Likewise,  dime  thy  laniline  or  a-dimethylamino- 

»  J.  Chem.  Soc.,  85,  398;     Ber.  d.  chem.  Ges.,  40,  3724. 

2  Ber.  d.  chem.  Ges.,  36,  2949. 

»  Acree  and  Slagle:  Amer.  Chem.  J.,  39,  534,  535. 


18 

a-bromnaphthalene  and  quinone  form  intensely  colored  quin- 
aminones  in  aqueous  solutions,  the  color  of  which  fades  to 
that  of  the  quinone  when  the  amine  is  converted  into  the 
salt. 

This  idea  is  further  borne  out  by  the  fact  that  Bistrzycki's 
diphenylquinoneme thane,1  which  can  not  form  the  quinone- 
phenolate  salt,  (C6H5)2C  :  C6H4  :  O,  is  far  less  deeply  colored 
than  the  salts  of  benzaurin,  C6H5C(  :  C6H4  :  O)(C6H4ONa), 
or  aurin,  (NaOC6H4)2C  :  C6H4  :  O,  which  can  form  the  intra- 
molecular, deeply  colored  quinonephenolate  group. 

Further  evidence  is  furnished  by  the  brilliant  work  of 
Baeyer,2  who  showed  that  salts  of  />-aminotriphenylcarbinol, 
(C6H5)2C  :  C6H4  :  NH2C1,  which  can  not  form  a  quinaminone, 
are  only  light  orange  in  color,  whereas  the  /?,/>-diaminotri- 
phenylcarbinol  gives  salts  having  an  intense  violet  color  be- 
cause it  forms,  to  some  extent,  the  deeply  colored  quinami- 
none group: 

(NH2C6H4)  (C6H5)C :  C6H4 :  NH2C1 


(NH2C6H4)  (C6H5)C  :  C6H4  :  NH2C1. 


When  an  excess  of  acids  is  added  to  fuchsin  or  to  malachite 
green3  the  colors  fade  because  the  acid  converts  the  amino 
group  into  a  salt  which  can  not  form  the  quinaminone. 

III.  The  equations  and  ideas  used  by  Hantzsch  and  Stieg- 
litz  to  express  the  affinity  constant  of  the  indicator  and  the 
tendency  to  form  the  colored  salts  are  not  complete4  and 
have  been  replaced  by  those  developed  by  Acree5  to  show 
the  relations  between  the  equilibrium  constants  and  the  af- 
finity constants  of  the  several  tautomeric  forms  of  the  acid. 
These  equations  have  been  tested  experimentally  in  the  ura- 
zole  series  by  Acree  and  Shadinger6  and  found  to  hold,  and 

»  Ber.  d.  chem.  Ges.,  36,  2337. 

2  Ann.  Chem.  (Liebig),  354,  161-2. 

3  Acree  and  Slagle:  Amer.  Chem,  J.,  39,  536. 

*  Acree:  Ibid.,  39,  529.     Stieglitz:  Ibid.,  39,  652.     Wegscheider:  Z.  Elek.  Chem.; 
34,  510.     Hildebrand:  J.  Am.  Chem.  Soc.,  30,  1914. 

6  Amer.  Chem  J.,  38,  11,  et  seq.,  and  many  subsequent  articles. 
«Ibid.,  39,  124. 


19 

similar  ideas  are  also  being  used  by  Wegscheider.  A  great 
deal  of  quantitative  work  will  be  necessary  to  clear  up  all 
of  these  problems  connected  with  the  indicators.  The  cause 
of  the  color1  is  probably  the  inter-  or  intramolecular  change  of 
the  -various  salts  into  each  other,  as  has.  been  brought  out  thor- 
oughly by  Hartley  and  Baly* 

In  the  last  year  or  two  a  number  of  others  have  begun 
work  from  this  point  of  view  that  the  chief  source  of  color  is 
not  the  quinone  group  but  a  quinonephenolate  group,  and 
that  the  most  important  source  of  the  color  is  probably  the 
intramolecular  salt  formed  by  the  union  of  the  quinone  and 
the  phenolate  or  aniline  derivative.  In  1907,  Baeyer3  pub- 
lished a  long  and  valuable  article  on  the  dyestuffs,  in  which 
he  gave  up  his  theory  of  halochromy  in  favor  of  the  quinone 
theory,  discussing  fully  his  reasons  for  doing  so.  He  proposed 
this  quinonephenolate  theory  and  tested  it  by  treating  fuch- 
sone  and  fuchsoneammonium  chloride  with  sodium  phenolate 
and  dime  thy  l-/>-toluidine,  but  no  colors  were  obtained.  My 
experiments,  however,  gave  beautiful  color  changes. 

Stieglitz4  has  also  given  up  his  former  point  of  view  and  now 
has  proposed  the  quinhy drone  hypothesis  as  a  cause  of  the 
color  changes,  including  the  salts  as  well. 

Willstaetter  and  Piccard,5  at  about  the  same  time,  brought 
out  in  a  valuable  contribution  the  same  quinhydrone  hy- 
pothesis and  applied  it  in  a  number  of  directions. 

Recently  K.  H.  Meyer6  has  discussed  some  of  the  recent 
work  and  ideas  and  prepared  a  number  of  compounds. 

Since  Acree's  first  paper  was  published  R.  Meyer7  has  pre- 
sented an  important  article  in  which  he  has  changed  from 
Baeyer's  theory  of  halochromy  to  the  quinonephenolate 
theory  which  I  am  using. 

Wegscheider8  too  has  recently  taken  up  the  study  of  phenol- 

1  Amer.  Chem.  J..  39,  537. 

2  J.  Chem.  Soc.,  85,  1029;  89,  502,  514;  91,  426,  1572. 
»  Ann.  Chem.  (Liebig),  354,  162. 

*  Amer.  Chem.  J.,  39,  651. 

6  Ber.  d.  chem.  Ges.,  41,  1458. 

«Ibid.,  42,  1149. 

7 /&«*.,  41,  2446. 

»  Z.  Elek.  Chem.,  34,  510. 


20 

phthalein  from  a  similar  point  of  view  and  has  obtained  re- 
sults in  harmony  with  this  theory. 

It  is  evident  then  that  a  number  of  men  have  been  engaged 
on  work  which  led  them  to  the  same  general  point  of  view, 
which  is  a  very  great  advance  in  the  theory  of  indicators 
and  dyestuffs.  I  do  not  claim  any  credit  for  the  very  im- 
portant view  advanced  by  Baeyer,  Stieglitz,  and  Willstaetter 
that  quinhydrones,  as  they  are  always  defined,  are  concerned 
in  the  colors  of  the  free  acids.  But  I  do  believe  that  this 
theory  of  tautomeric  salts  accounts  more  fully  for  the  colors 
of  the  salts  and  their  alkylation  reactions  than  the  theory  of 
any  other  worker,  and  since  the  salts  are  the  substances  of 
chief  importance  in  the  colors  and  reactions  of  dyestuffs, 
the  free  acids  or  bases  being  comparatively  insignificant  in 
this  respect,  I  shall  devote  my  attention  chiefly  to  this  phase 
of  the  subject. 

A  study  of  the  affinity  constants  of  the  indicators  from  this 
point  of  view,  of  the  influence  of  alcohol  in  decolorizing  the 
salts,  of  the  influence  of  salts  and  acids  in  intensifying  the 
colors  of  the  dyestuffs,1  and  other  problems  mentioned  in  my 
first  article  are  of  very  great  importance.  The  salts  of  weak 
bases,  such  as  SnCl2,  A1C13,  etc.,  and  also  acids,  seem  to  form 
deeply  colored  double  compounds  with  a  number  of  quinoid 
and  lactoid  derivatives.  I  suspect  that  in  all  such  cases 
the  basic  properties  of  the  oxygen  of  a  quinone  group  are 
directly  concerned. 


The  melting  point  method  can  not  be  used  as  a  criterion  of 
the  purity  of  fluorescein.  It  decomposed  above  290°  with- 
out melting.  Every  precaution  was  therefore  taken  in  the 
preparation  to  obtain  a  pure  substance.  Pure  phthalic  an- 
hydride and  pure  resorcinol  were  heated  with  zinc  chloride 
at  1  80°.  The  product  was  obtained  free  from  resorcinol 
by  washing  with  several  liters  of  cold  water,  and  was  then  dis- 
solved in  a  solution  of  sodium  carbonate  and  precipitated 
by  sulphuric  acid.  The  fluorescein  obtained  in  this  way  is 

1  K.  H.  Meyer:  Ber.  d.  chem.  Ges.,  41,  2568.     Meyer  and  Hantzsch:  Ibid.,  40, 
3479. 


21 

bright  yellow  in  color.  After  it  is  crystallized  a  number  of 
times  from  alcohol  it  becomes  dark  red,  a  darker  red  than 
sulphophenolphthalein.  When  the  yellow  product  is  heated 
in  an  air  bath  for  five  hours  at  115°  it  shows  no  appearance 
of  red  whatever.  This  bright  yellow  color  is  retained  even 
after  standing  in  a  glass- stoppered  bottle  eighteen  months. 

The  Four  Ethyl  Esters  of  Fluorescein. 

The  four  ethyl  esters  of  fluorescein  were  obtained  by  dis- 
solving fluorescein  in  alcoholic  sodium  hydroxide,  adding 
ethyl  iodide,  and  heating  under  a  reflux  condenser  on  the 
water  bath.  Different  amounts  of  fluorescein,  solvent,  and 
halide  were  used  and  the  time  of  alkylation  varied  from  four 
to  twenty-four  hours.  No  definite  conclusions  were  reached 
as  to  the  amounts  of  the  different  esters  formed  under  the 
different  conditions.  The  best  yield  of  esters  however,  was 
obtained  by  continuing  the  alkylation  eight  hours. 

After  the  reaction  was  over  any  excess  of  ethyl  iodide  was 
expelled  by  evaporation  and  the  product  was  poured  into 
cold  water,  whereupon  the  two  diethyl  esters  were  precipi- 
tated. These  were  then  filtered  and  carbon  dioxide  was  passed 
into  the  filtrate.  This  precipitated  the  two  monoethyl  esters. 

The  only  method  found  for  separating  the  two  monoethyl 
esters  was  fractional  crystallization  from  dilute  alcohol.  After 
repeated  crystallizations  the  colored  carboxyl  ester,  some- 
what more  soluble  in  dilute  alcohol  than  the  colorless  phenol 
ester,  was  obtained  with  a  constant  melting  point  247°.  The 
colorless  phenol  ester  was  found  to  melt,  when  pure,  at  251°. 

The  colored  diethyl  ester  was  separated  from  the  colorless 
diethyl  ester  also  by  fractional  crystallization  from  dilute 
alcohol.  When  pure,  the  colorless  diethyl  ester  melts  at 
182°,  and  the  colored  diethyl  ester  at  159°. 

As  stated  above,  Herzig  and  Pollak,  on  methylating  fluor- 
escein salts  with  methyl  iodide,  obtained  chiefly  the  lactoid 
esters.  I  have  found,  in  general,  that  ethyl  iodide  also 
produces  the  lactoid  esters  in  excess,  although  the  ratio  of 
the  lactoid  to  the  quinoid  varies  greatly  with  the  conditions 
of  the  experiment  and  time  of  alkylation.  Quite  different 


22 

results  were  obtained  with  diazomethane;  Herzig  and  Pollak 
obtained  with  this  reagent  chiefly  the  quinoid  esters. 

I  have  found  that  diazoethane  yields,  with  an  excess  of 
either  the  red  and  yellow  fluorescein,  only  the  colored  quinoid 
diethyl  ester.  The  product  of  the  reaction,  without  purifica- 
tion, melts  at  157°,  only  two  degrees  below  the  melting 
point  of  the  pure  ester,  159°.  When  this  ester  is  crystal- 
lized from  glacial  acetic  acid  it  gives  the  proper  melting  point 

Preparation  of  the  Pure  Sodium  Salt  of  the  Phenol  Ethyl  Ester 
of  Fluorescein. 

The  pure  sodium  salt  of  the  phenol  ethyl  ester  was  prepared 
by  agitating  an  excess  of  the  ester  with  a  solution  of  sodium 
hydroxide  and  then  filtering  the  undissolved  ester.  The 
filtrate  was  shaken  again  with  a  little  of  the  ester  and  filtered. 
The  filtrate  was  extracted  with  carbon  tetrachloride  and  then 
evaporated  to  dry  ness  on  the  water  bath.  There  is  no  loss 
in  weight  on  evaporating  this  salt  to  dry  ness  on  the  water 
bath,  although  some  of  the  esters  are  slightly  volatile  under 
these  conditions. 

The  sodium  salt  of  the  phenol  ester  dissolves  in  water  with 
a  color  much  less  intense  than  that  of  the  fluorescein  salt, 
and  in  ethyl  and  methyl  alcohol  with  a  very  faint  color  at 
temperatures  from  — 15°  to  o°.  This  color  increases  very 
decidedly  as  the  temperature  is  raised  to  80°,  but  decreases 
again  as  the  temperature  is  lowered. 

An  attempt  was  made  to  study  the  velocity  of  ester  forma- 
tion; the  equation  for  the  reaction  is  that  of  the  second  order 

~x — A N"   .rl/v  . 

t(A-x-) 

The  concentrations  of  the  sodium  salt  and  ethyl  iodide 
were  0.3  weight  normal  and  volume  normal,  respectively, 
in  40  per  cent  alcohol. 

The  solution  was  sealed  in  a  tube  and  heated  in  a  constant 
temperature  bath  at  60°. 

In  the  following  table  t  gives  the  time  in  hours,  A  the  num- 
ber of  grams  of  salt  taken,  x  the  amount  of  ester  formed, 


23 

and  A — x  the  amount  of  unchanged  salt.     AK  is  the  con- 
stant calculated  for  a  bimolecular  reaction. 

/.  A.  A  —  x.  x.  AK. 

2  0.382  0.3169  0.0651  0.10 

3  03053       0.0767        0.19 

4  0.2492       0.1328        0.13 
7  0.2028       0.1792        0.12 

(17)  0.0190  0.3630  o.n 

(24)  0.0544  0.3276  (0.25) 

The  divergence  of  AK  from  a  constant  value  is  due  to  the 
difficulty  in  obtaining  quantitative  methods  of  separation 
and  analysis. 

I  found  that  on  ethylating  the  sodium  salt  as  above,  a 
mixture  of  the  colorless  phenol  diethyl  ester  and  the  colored 
quinone  diethyl  ester  is  formed.  To  separate  and  identify 
these  esters  I  boiled  the  alkylation  product  about  three 
hours  in  alkali,  which  saponified  the  colored  quinone  diethyl 
ester.  The  solution  was  then  filtered,  the  filtrate  acidified, 
the  phenol  ethyl  ester  extracted  with  carbon  tetrachloride, 
and  identified  by  its  melting  point,  247°. 

The  unsaponified  colorless  phenol  diethyl  ester  was  col- 
lected from  the  filter  and  identified  by  the  melting  point, 

251°. 

In  order  to  determine  whether  any  rearrangement  of  the 
esters  took  place  under  the  conditions  of  the  experiment, 
I  dissolved  0.0524  gram  of  the  colorless  phenol  ester  and 
0.5500  gram  of  the  colored  quinone  ethyl  ester  in  5 
cc.  of  40  per  cent  alcohol  with  ethyl  iodide  in  o .  3  N  solution 
of  40  per  cent  alcohol  and  heated  the  mixture  a  number  of 
hours  in  a  sealed  tube  in  the  bath  at  60°.  The  tube  was  then 
opened  and  after  separation  0.0516  gram  of  the  colorless 
phenol  ethyl  ester  and  0.5494  gram  of  the  colored  quinone 
ethyl  ester  were  recovered.  I  then  dissolved  0.6024  gram 
of  the  sodium  salt  of  the  phenol  ethyl  ester,  0.0316  gram  of 
the  colorless  phenol  ethyl  ester,  and  0.1702  gram  of  the  col- 
ored quinone  ethyl  ester  in  40  per  cent  alcohol,  sealed  this 
solution  in  a  tube,  and  heated  at  60°  for  six  hours.  The  tube 
was  then  opened  and  the  esters  extracted  from  the  salt.  After 


24 

the  separation  0.0306  gram  of  the  colorless  phenol  ethyl 
ester  and  0.1698  gram  of  the  colored  quinone  ethyl  ester 
were  recovered. 

Conclusions  from  the  Alkylations. 

Since  the  colorless  phenol  diethyl  ester  and  the  colored 
quinone  diethyl  ester  are  formed  from  the  sodium  salt  of  the 
phenol  ethyl  ester  and  since  we  have  found  that  no  rear- 
rangement takes  place  under  the  conditions  of  the  experi- 
ment, the  equilibrium  and  reactions  can  be  expressed  as  fol- 
lows: 


OC/        lN>C(C6H8OC2H5)(C6H3ONa)   ^± 
\  0  /       J o 1 

OC/       4\C(C6H3OC2H5)(C6H30)  +  Na  +  C2H5I  ^±: 

W\  o  /       i O l 
/C6H4X 
OC<  >C(C6H3OC2H5)  (C6H3OC2H5) 

\  o  '        J O l 

(C2H6OC6HS) (O :  C6H3 :  )CC6H4COONa  ^± 

(C2H5OC6H3)(0:C6H3:)CC6H4COO  +  Na  +  C2H5I  ^± 

(C2H5OC6H3)(O:C6H3:)CC6H4COOC2H5  +  Nal. 
i o — -J 

The  equilibrium  is  assumed  to  be  between  the  molecular 
forms  of  the  salts  because  the  evidence  obtained  in  work 
on  the  urazoles  seems  to  point  in  this  direction.  The  same 
is  true  of  the  assumption  of  a  reaction  between  the  alkyl 
halide  and  the  anions  of  the  salt.  It  has  been  shown  in  work 
in  other  fields  that  reaction  mechanisms  are  sometimes  very 
complex  and  I  do  not  commit  myself  finally  as  to  the 
above  assumptions. 


Phenolphthalein    was    obtained     quite     pure,     melting     at 
254°,  by  the  method  of  McCoy.1 

i  Amer.  Chem.  J.,  81.  507. 


25 

The  attempt  to  obtain  the  four  esters  of  phenolphthalein 
in  sufficient  quantity  and  purity  by  direct  alkylation  of  phenol- 
phthalein in  alkaline  solution  with  ethyl  iodide  proved  fruit- 
less. The  potassium  salt  of  phenolphthalein  was  treated 
with  sulphonyl  chloride.  The  reaction  was  vigorous,  sulphur 
dioxide  being  evolved.  The  product  of  the  reaction,  resem- 
bling tar,  was  readily  soluble  in  ether  and  gave  a  purple  color 
with  alkali  but  was  not  obtained  pure. 

TETRABROMPHENOLPHTHALEIN. 

Since  the  tetrabromphenolphthalein  and  its  derivatives 
were  more  readily  obtained  pure,  attention  was  directed 
to  them. 

Phenolphthalin  was  prepared  according  to  the  directions 
of  Baeyer.1  This  can  be  obtained  quite  free  from  phenol- 
phthalein by  crystallization  from  boiling  water:  100  parts 
of  water  dissolve  at  20°  0.0175  parts  of  phenolphthalin. 
When  pure  it  melts  at  225°  and  dissolves  in  alkali  entirely 
without  color.  It  is  not  changed  appreciably  on  standing, 
but  by  prolonged  heating  in  air  it  is  oxidized  to  phenolphthal- 
ein. 

In  all  of  the  following  solubility  experiments  a  known 
quantity  of  the  acid  or  ester  was  shaken  in  a  machine  with  a 
known  quantity  of  alkali,  not  sufficient  for  solution,  at  20°, 
for  a  number  of  hours.  The  undissolved  acid  or  ester  was 
filtered  and  weighed.  The  filtrate  was  acidified  and  the 
precipitated  material  also  weighed  as  a  check. 

Meyer  and  Spengler2  found  that  the  unsubstituted  phthal- 
eins  neutralize  two  molecular  equivalents  of  alkali.  My 
results  with  the  phthaleins  verify  this.  But  the  phthalins 
require,  in  general,  somewhat  less  than  two  molecular  equiva- 
lents of  alkali,  instead  of  the  calculated  three  molecules,  a 
proof  that  the  phthalins  are  much  weaker  acids  whose  salts 
are  more  greatly  hydrolyzed.  Since  it  is  proposed  to  measure 
the  affinity  constants  of  a  large  number  of  these  dyestuffs  a 
preliminary  study  of  the  hydrolysis  constants  through  a  de- 

i  Ann.  Chem.  (Liebig),  202,  80. 
*  Ber.  d.  chem.  Ges.,  38,  1327. 


26 

termination  of  the  solubilities  of  these  substances  in  alkalies 
seemed  desirable. 

Solubility  of  Phenolphthalin  in  Alkali. 

Calculated  cc.  of  0 . 1  N 

Amount  of  acid  NaOH,  one  molecular  equiva-  cc.  of  NaOH 

dissolved.  lent  to  one  of  acid.  required. 

i-3205  4I-3          29.22 

0.4901  15.3  10.78 

The  small  amount  of  alkali  required  for  the  solution  of 
phenolphthalin  can  be  explained  by  the  formation  of  an  acid 
salt  in  solution. 

I  prepared  tetrabromphenolphthalin  by  Baeyer's 
method.1  It  crystallizes  from  benzene  in  colorless  short 
needles  which  melt  at  2o8°-2O9°,  When  exposed  to  the 
light  in  a  glass- stoppered  bottle  for  several  months  it  becomes 
colored  light  pink,  without,  however,  any  change  in  the  melt- 
ing point. 

Solubility  of  Tetrabromphenolphthalin  in  Alkali. 

Calculated  cc.  of 
0.1  N  NaOH,  two 

Amount  of  acid  molecular  equivalents  cc.  of  NaOH 

dissolved.  to  one  of  acid.  required. 

0.7614  9.12  7.48 

0.4731  7-06  5.49 

It  appears  from  this  experiment  that  an  acid  salt  is  formed 
in  this  case. 

The  carboxyl  ester  of  phenolphthalin  was  obtained  by 
passing  hydrogen  chloride  into  an  alcoholic  solution  of  the 
acid.  This  ester  crystallizes  from  dilute  alcohol  in  colorless 
leaves  which  melt  at  i57°-i58°.  The  ester  is  quite  stable, 
being  saponified  only  to  a  slight  extent  by  standing  over- 
night in  a  ten  per  cent  solution  of  sodium  hydroxide. 

The  carboxyl  ester  of  phenolphthalin  was  brominated  by 
dissolving  it  in  glacial  acetic  acid  and  adding  bromine.  The 
tetrabrom  product  crystallizes  from  glacial  acetic  acid  and 
melts  at  164°. 

»  Ann.  Chem.  (Liebig);  202,  85. 


27 

Solubility    of    the    Carboxyl    Ethyl    Ester    of    Tetrabromphenol- 
phthalin  in  Alkali. 

Calculated  cc.  of 
0.1  N  NaOH,  two 

Amount  of  acid  molecular  equivalents  cc.  NaOH 

ester  dissolved.  to  one  of  acid  ester.  required. 

0.4804  14.46  15.95 

0.3160  9.52  10.58 

I  found  that  potassium  dichromate  had  no  oxidizing 
effect  on  this  ester.  Potassium  permanganate  and  potas- 
sium ferricyanide  readily  oxidize  it  to  the  salt  of  the  carboxyl 
ester  of  tetrabromphenolphthalein.  The  free  ester  was  not 
obtained  from  this  salt  in  sufficient  quantity  and  purity  for 
the  investigation. 

I  prepared  /?-oxy-o-benzoylbenzoic  acid  according  to 
Friedlander's  directions,1  and  the  carboxyl  ethyl  ester  by 
passing  hydrogen  chloride  into  the  alcoholic  solution.  The 
ester  crystallizes  from  glacial  acetic  acid  as  a  white  crystal- 
line powder  melting  at  115°. 

I  attempted  to  bring  about  the  condensation  of  this  ester 
with  phenol  in  the  presence  of  zinc  chloride  and  also  of  con- 
centrated sulphuric  acid  in  order  to  obtain  the  carboxyl  ethyl 
ester  of  phenolphthalein,  but  was  unsuccessful. 

The  attempt  to  prepare  the  silver  salts  of  the  carboxyl 
ethyl  ester  of  phenolphthalein  and  the  carboxyl  ethyl  ester  of 
tetrabromphenolphthalein  proved  a  failure.  A  water  solution 
of  silver  nitrate  was  added  to  a  water  solution  of  each  salt 
at  o°  in  a  vessel  of  actinic  glass,  but  in  each  case  silver  oxide 
separated  and  no  trace  of  the  silver  salt  was  formed. 

/>-OXYDIPHKNYLPHTHAUD.  2 


^v        /C6H5 
/?-Oxydiphenylphthalid,    OC^  >C<  ,      should, 

^   O  /     XC6H4OH 
from  the  theory,  yield  one  colorless  ester  and  one  colorless 
salt. 

This  substance  was  prepared  according  to  Baeyer's  method, 
by  condensing  phenol  and  benzoylbenzoic  acid  with  concen- 

i  Ber.  d.  chem.  Ges.,  26,  172. 
a  Ann.  Chem.  (Liebig),  364,  162. 


28 

trated    sulphuric    acid    and    crystallizing    the    product    from 
glacial  acetic  acid.     It  melted  at  164°. 

Solubility  oj  p-Oxydiphenylphthalid  in  Alkali. 

Calculated  cc.  of 
0.1  N  NaOH,  one 

Amount  of  acid  molecular  equivalent  cc.  NaOH 

dissolved.  to  one  of  acid.  required. 

0.1044  3.46  H-34 

0.0700  2.32  7.28 

That  this  acid  is  extremely  weak  and  the  salt  highly  hy- 
drolyzed  is  shov,  n  by  the  excess  of  alkali  above  the  calculated 
required  for  solution. 

The  sodium  and  potassium  salts  of  />-oxydiphenylphthalid 
are  precipitated  from  a  water  solution  by  the  addition  of  an 
excess  of  a  concentrated  solution  of  sodium  or  potassium 
hydroxide  but  it  was  found  impossible  to  obtain  either  of 
these  salts  for  analysis  free  from  alkali.  The  attempt  to  iso- 
late other  metallic  salts  also  proved  futile. 

A  colorless  oil  was  formed  by  heating  a  solution  of  the 
£-oxydiphenylphthalid  in  absolute  alcohol  with  sodium  wire 
but  was  not  obtained  pure.  No  salt  was  formed  on  boiling 
a  solution  of  the  acid  in  anhydrous  ether  with  sodium  wire 
for  five  hours. 

I  experienced  the  same  difficulty  in  attempting  to  iso- 
late the  alkali  salts  of  benzo-/>-cresophthalein. 

On  methylating  ^-oxydiphenylphthalid  with  methyl  iodide 
and  alcoholic  sodium  hydroxide  a  colorless  ester  was  obtained, 
but  not  in  pure  condition. 

DIBROM-/>-OXYDIPHENYI,PHTHAIvID. 

/?-Oxydiphenylphthalid  was  dissolved  in  glacial  acetic 
acid,  at  about  60°,  and  a  solution  of  bromine  in  glacial  acetic 
acid  was  added.  On  cooling  the  solution,  the  dibrom-p- 
oxydiphenylphthalid  separated  out.  On  crystallization  from 
acetic  acid  this  was  obtained  pure  in  white  crystals  which 
melt  at  199°. 

The  methyl  ester  prepared  with  diazomethane  gave  on 
analysis  the  following  results: 


29 

Calculated  for  Found. 

C2iHi5O3Br2.  (Carius  method.) 

Br 33.75  I-  33-48 

n.  33-24 

Dibrom-/>-oxydiphenylphthalid  was  methylated  by  alco- 
holic sodium  hydroxide  and  methyl  iodide.  The  methyl 
ester  was  obtained  as  a  white  powder  which  crystallizes 
readily  from  glacial  acetic  acid  and  melts  at  157°. 

By  methylating  the  dibrom-/>-oxydiphenylphthalid  with 
diazomethane  an  identical  ester  was  obtained,  melting  at 
157°.  No  lowering  of  the  melting  point  was  produced 
on  fusing  a  mixture  of  these  esters. 

These  experiments  seem  to  prove  very  clearly  that  the 
sodium  salt  and  the  free  acid  have  the  same  constitution, 
that  of  the  lactoid  form,  and  give  evidence  that  the  theory 
of  tautomeric  salts  is  correct. 

EXPERIMENTS   WITH  THE   DII^ATOMETER. 

It  seemed  likely  that  the  affinity  constants  of  these  weak 
acids  might  be  determined  by  the  use  of  the  dilatometer,1 
provided  no  salt  effect  interferes.  This  method  depends  on 
the  reversible  reaction  involved  in  the  condensation  of  ace- 
tone, and  the  splitting  of  the  diacetone  alcohol  thus  formed 
into  two  molecules  of  acetone.  The  expansion  of  the  solu- 
tion due  to  the  change  of  the  diacetone  is  generally  measured. 
This  reaction  is  catalyzed  by  the  presence  of  hydroxyl  ions 
and  the  velocity  is  proportional  to  the  concentration  of  these 
ions. 

The  diacetone  alcohol  was  prepared  by  extracting  pure 
calcium  hydroxide  in  a  Soxhlet  extractor  with  acetone,  ac- 
cording to  Hofmann's  method.  The  solution  was  freed  from 
water  and  acetone  by  distilling  it  under  diminished  pressure 
and  was  then  fractionated.  The  solutions  measured  contained 
from  two  to  ten  per  cent  of  the  diacetone  alcohol  in  conduc- 
tivity water.  A  solution  of  diacetone  alcohol  in  conductivity 
water  showed  no  appreciable  change  after  standing  several 
months.  The  measurements  were  made  in  a  constant  tem- 

i  Koelichen:  Z.  physik.  Chem.,  33,  132. 


30 

perature  bath  at  25°.     The  variation  during  the  experiment 
was  only  o°.oi. 

Velocity  constants  for  sodium  hydroxide  having  a  concen- 
tration of  N/io,  N/20,  N/40,  N/8o,  and  N/i6o  in  the  dila- 

tometer  were  obtained  from  the  equation  for  the  reaction  of 
A 

the   first   order,  —— r-  =  K.     The    results   are    given   in 

t(A  — x) 

Tables  I.-V.,  inclusive. 

Equal  volumes  of  ten  per  cent  diacetone  alcohol  and  alkali 
of  the  proper  strength  to  give  the  above  concentrations  were 
used.  In  the  tables  t  is  the  time  in  minutes,  A  the  total  ex- 
pansion in  divisions  on  the  dilatometer  stem,  and  K  the  veloc- 
ity constant. 

Table  I. — o.i  N  Sodium  Hydroxide.     A  =  68.1. 

t.  A—x.  K.  t.  A.  —  X.  K. 

10    40.0    0.0224         30     14.2    0.0224 
15    30.8    0.0226         40     8.4    0.0225 

2O  24.2  O.O22I  50  4.8  O.O224 

25          18.4         0.0223 

Mean,  0.0224 

Table  II. — 0.05  N  Sodium  Hydroxide.  A  =  36.0. 

t.  A — x.  K.  t.  A  —  X. 

5  31.3  0.0119  50  9.6 

15  23.9  0.0116  55  8.5 

25  18.4  0.0117  85  3.8 

35  13  9  0.0118 

Mean,  0.0116 

Table  HI. — 0.025  .V  Sodium  Hydroxide.     A  =  44.2. 

t.       A  —  x.         K.  t.       A—x.          K. 

30      29.5      0.00585          100       12.0      0.00575 
40       25.7       0.00589  120        9.4       0.00572 

60     20. o    0.00574       I5°     6.4    0.00577 
80    15.5    0.00571 

Mean,  0.00578 

Table  IV. — 0.0125  N  Sodium  Hydroxide.     A  =  4.1.2. 

t.  A  —  x.  K.  t.  A—x. 

10  38.6  0.00273  100  22.6 

30  34.2  0.00270  130  19.0 
50  30.2  0.00270  160  16.0 
70  27.3  0.00270 

Mean,  0.00270 


Table  V. — 0.00625  N  Sodium  Hydroxide.     A  =  48.0. 

t.  A  —  x.  K.  t.  A—x.  K. 

20    45-5     0.00117       200     29.0    0.00119 
50    41.9     0.00118       260     24.8     o.ooiio 
80    38.9    0.00116       320     21.5     0.00119 
140    33  5     o. ooi 12 

Mean,  o. 00116 

Dilatometer  Measurements  of  Solutions  of  Phenolphthalein. 
— The  pure  sodium  salt  of  phenolphthalein  was  prepared  by 
shaking  an  excess  of  the  acid  with  alkali  a  number  of  hours 
and  carefully  filtering  out  the  excess  of  acid.  A  portion  of 
the  filtrate  containing  0.400  gram  of  the  disodium  salt  was 
placed  in  the  dilatometer  with  an  equal  volume  of  ten  per 
cent  diacetone  alcohol.  In  Tables  VI.  and  VII.,  A  has  been 
calculated  only  approximately  from  a  number  of  experiments. 


K. 

o . 000023 
0.000022 

O . OOOO2 I 


Table  VI.- 

—A  «=  100. 

t. 

A  —  x. 

K. 

t. 

A  —  x. 

1480 
1900 
2620 

92  .6 

89.6 
87.6 

0.000022 
O.OOOO22 

o  .  000023 

3280 
4150 
4900 

83.5 
80.8 
78.1 

Mean,  0.000022 
Table  VII.— A  =  100. 

t.  A  —  x.         K.  t.  A—x.         K. 

960  92.9  0.000023  3420  83.6  0.000022 

1830  90.2  O.OOOO23  4080  80.6  O.OOOO22 

2250  89.4  O.OOOO2I  6140  69.2  O.OOOO24 


Mean,  0.000022 

This  volume  for  Ktrans  corresponds  to  a  hydroxyl  ion  con- 
centration of  0.00012  N.  If  we  take  as  the  concentration  of 
the  phenolphthalein  in  saturated  solution  the  value  0.0012  N 
found  by  McCoy1  and  remember  that  the  solution  of  the  phenol- 
phthalein salt  is  diluted  with  an  equal  volume  of  the  solution 
of  diacetone  alcohol,  we  should  obtain  2  X  io~7  for  the  hy- 
drolysis constant,  or  0.6  X  io~7  for  the  affinity  constant  of 
phenolphthalein.  This  is  much  larger  than  the  values  ob- 

lAmer.  Chem.  J.,  81,  511. 


tained  by  Salm,  McCoy,  Hildebrand,  and  Wegscheider  and 
shows  most  decidedly,  as  do  Tables  VIII.  to  XI.,  inclusive, 
that  the  phenolphthalein  salt  lowers  the  catalytic  effect  of  the 
hydroxyl  ions  very  materially.  Unless  some  means  can  be 
found  to  obviate  this  the  method  can  not  be  used  to  deter- 
mine the  affinity  constants  of  these  indicators  and  related 
compounds. 

Solutions  of  phenolphthalein  were  then  prepared  by  dis- 
solving a  definite  amount  of  the  acid  in  a  sodium  hydroxide 
solution  containing  varying  amounts  of  the  alkali.  Dilatom- 
eter  measurements  were  made  with  these  solutions.  The 
results  are  given  in  Tables  VIII.  to  XI.,  inclusive.  It  is  seen 
that  the  velocity  constant  decreases  with  increase  in  the 
amount  of  phenolphthalein  present. 

In  the  following  tables,  the  amounts  of  alkali  used  are 
expressed  in  molecular  equivalents  for  one  molecular  equivalent 
of  acid: 


Table  VIII. — 4.6  N/40  NaOH.     A  =  50.5. 


10 

20 

30 
40 


A — *. 

45-9 
41.6 

37-8 

34-2 


K. 

o . 00424 
o . 00420 

0.00429 

o . 00423 


60 

80 

120 


A  —  x. 
28.2 
22.8 
15-4 


K. 


o . 0042 i 
o . 0042 i 

0.00429 


Mean,  0.00424 


Table  IX.— 20  N/io  NaOH.     A  =  34.2. 


t. 

A—  *. 

K. 

8 

24.2 

0.0187 

12 

20-3 

0.0188 

16 

I7.I 

0.0187 

20 

14-5 

0.0186 

I. 

24 
28 

36 


A—x. 

12.  I 

10.2 

7.2 


K. 

0.0187 
O.OI87 
0.0187 


Mean,  0.0187 


Table  X.—4O  N/io  NaOH.     A  =  28.8. 


t 

12 

15 
20 

24 


A — x. 

15-9 
13-8 
IO-9 

8.9 


K. 

0.0215 
0.0213 
O.O2IO 
O.O2I2 


t. 

28 
38 

49 


A — * 

7-3 
4-5 
3-4 


K. 

0.0212 
0.0212 
O.O2IO 


Mean,  0.0212 


Table  XL— 70  N/2O  NaOH.     A  =  34.3. 


*. 

A—x. 

K. 

5 

30.0 

0.0116 

10 

26.5 

O.OII2 

15 

23.1 

0.0114 

20 

20.  6 

O.OIIO 

30 
40 
50 


A—x. 

15-9 

"•5 

9-6 


O.OIIO 

0.0118 
o . 1009 


Mean,  0.0113 

of     p-Oxydiphenyl- 


Dilatometer    Measurements     o)    Solutions 

phthalid. 

These  solutions  were  prepared  by  dissolving  the  acid  in 
varying  amounts  of  caustic  soda.  The  results  of  the  dilatom- 
eter  measurements  are  given  in  Tables  XII.  to  XIV.,  inclusive. 
The  same  salt  catalysis  is  noticed  in  this  case  as  with  phenol- 
phthalein.  This  salt  catalysis  was  noticed  by  Koelichen, 
who  found  that  some  salts  acted  as  negative  and  others  as 
positive  catalyzers. 


t. 

8 
16 
24 
32 


Table  XII.— 20  N/io  NaOH.     A 


A—x. 

28.3 
23.2 
I8.7 
15-3 


K. 

O.OII2 
O.OIIO 
O.OII2 
O.OIII 


40 
56 


Mean,  0.0112 


Table  XIII. — 40  N/io  NaOH.     A  =  32.3. 


t. 

A  —  x. 

K. 

5 

25-3 

O.O2I2 

10 

19  9 

O.02IO 

15 

15-5 

O.O2I2 

20 

1  1.  8 

0.0218 

30 
40 
60 


A—x. 

7-7 
7-7 

2.O 


O.02I8 

0.0218 

0.0217 


Mean,  0.0215 


Table  XIV.— 80  N/io  NaOH. 

t.  A—x.  K.  t. 

5  25.8  0.0229  25 

10  19.9  0.0227  30 

15  15.1  0.0229  40 

20  11.7  0.0229 


Mean,  0.0228 


34 

The  above  results  for  the  various  concentrations  of  sodium 
hydroxide,  phenolphthalein,  and  £-oxydiphenylphthalid  are 
shown  in  Fig.  I.,  plotted  in  the  form  of  a  curve. 


0.05- 


0.00626- 


3,0       30        *fO      v5'O        (.0       70 


?0      /CO 


The  abscissas  represent  the  velocity  constants,  K,  and  the 
ordinates  the  normality  of  the  original  alkaline  solutions. 
Curve  A  shows  the  results  for  sodium  hydroxide  (the  devia- 
tion of  A  from  a  straight  line  is,  of  course,  due  to  the  suppressed 
ionization  at  the  higher  concentrations) ;  curve  B  shows  the 
results  obtained  with  the  phenolphthalein  solutions;  and  C, 
those  obtained  with  solutions  of  />-oxydiphenylphthalid. 
The  decrease  in  the  velocity  contant  due  to  the  presence  of 
the  phthalein  or  phthalid  salt  is  very  clearly  shown,  the  de- 
crease being  greater  in  the  case  of  />-oxydiphenylphthalid, 
C,  than  in  the  case  of  phenolphthalein,  B. 


35 

A  New  Dtiatometer. 

It  is  readily  seen  that  the  glass  dilatometer  as  devised  by 
Koelichen  is  not  sufficiently  sensitive  for  studying  very  di- 
lute solutions  of  alkali  nor  for  the  very  accurate  investiga- 
tion of  this  salt  catalysis.  An  attempt  was  made  to  obtain 
a  more  sensitive  instrument  by  following  the  plan  used  by 
Prof.  Morse  in  his  work  on  osmotic  pressure. 

A  brass  cell  (Fig.  II.)  was  made,  with  a  capacity  of  25  cc. 
and  an  internal  diameter  of  17  mm.,  the  wall  being  2  mm. 
thick.  The  cell  was  uniformly  nickel-plated  inside  and  out- 
side. It  was  closed  by  a  brass  cone  (b)  into  which  was  fastened 
with  Wood's  metal  (c)  an  open  manometer  tube,  etched  in 
i  mm.  divisions,  and  having  a  bore  of  0.5  mm.  diameter. 
A  small  platinum  tube  (d)  opening  within  the  cell,  by  the  side  of 
the  manometer,  was  also  fastened  into  the  cone.  This  small 
tube  could  be  closed  with  a  screw  cap  (e). 

The  cap  was  used  to  regulate  the  height  of  the  liquid  in  the 
manometer  before  the  measurements  were  taken.  When  a 
measurement  was  to  be  taken  the  manometer  tube  was  filled 
with  pure  water.  The  diacetone  alcohol  and  alkaline  solution 
were  brought  to  the  proper  temperature,  thoroughly  mixed, 
and  then  poured  into  the  cell.  The  cone  containing  the  manom- 
eter was  then  quickly  placed  in  the  cell  and  tightened  by 
the  threaded  brass  collar  (g).  The  superfluous  liquid  was 
allowed  to  escape  from  the  small  platinum  tube  until  the 
meniscus  was  at  the  proper  height  in  the  manometer  tube 
and  the  screw  cap  was  then  tightly  closed.  It  was  found  im- 
practicable to  use  washers  of  any  kind  between  the  cone  and 
the  cell  at  (/),  as  their  slightest  contraction  or  expansion  caused 
a  change  in  the  volume  of  the  cell  and  hence  an  error  in  reading. 
A  watertight  connection  was  obtained  at  this  point  (/)  by  the 
use  of  a  thin  layer  of  a  mixture  of  vaseline  and  the  lubricant 
obtained  by  melting  together  rubber  and  paraffine. 

During  the  measurements,  which  lasted  from  three  to  nine 
hours,  the  instrument  was  immersed  so  that  the  meniscus  was 
at  a  constant  level  in  a  constant  temperature  bath.  The 


36 

temperature  must  be  carefully  regulated  as  a  change  of  more 
than  o°.(X>5  of  a  degree  causes  considerable  error  in  reading. 


Fig.  II. 


A  number  of  improvements  have  suggested  themselves 
while  working  with  this  instrument,  yet  the  advantages  of  the 
present  type  over  the  glass  dilatometer  are  evident.  This 


37 

cell,  when  placed  in  the  bath,  will  attain  temperature  equilib- 
rium in  two  to  three  minutes.  The  following  tables  will 
show  the  degree  of  accuracy  that  can  be  attained.  In  these 
measurements  a  2  per  cent  solution  of  diacetone  alcohol  was 
used. 

Table  XV. — 0.0483  N  Sodium  Hydroxide.     A  =  14.29. 
t.  A  —  X.  K.  t.  A—X. 

2  13.57  O.OII23  31  6.41 

4  12.89          0.01120  41  4.95 

6  12.23  0.01126  51  3.83 

21  9.32  O.OII2I  6l  2-95 

26  7.13          0.01126 

Mean,  0.01123 

Table  XVI. — 0.0227  N  Sodium  Hydroxide.     A  =  22.80. 

t.  A—x.  K.  t.  A—x.  K. 

10  20.10  0.005673  35  14.50  0.005670 
15  18.39  0.005677  50  11.92  0.005671 

20  17.63  0.005679  60  10.46  O.O05672 

25  16.52  0.005672  70  9.18  0.005672 

30  1547  0.005678 

Mean,  0.005675 

These  are  remarkably  good  constants  and  serve  to  show 
how  accurate  our  chemical  methods  can  be  made.  Doubtless 
many  other  reactions  can  be  studied  by  such  methods  and  it  is 
hoped  that  this  work  will  be  continued. 


BIOGRAPHICAL. 

Edgar  Apple  Slagle  was  born  at  Cessna,  Bedford  Co.,  Pa., 
February  19,  1883.  He  received  his  preliminary  education  at 
the  private  school  of  Miss  Martha  E.  Grove,  Hanover,  Pa. 
He  was  graduated  from  Mercersburg  Academy,  Mercersburg, 
Pa.,  in  the  Latin  Scientific  course,  in  June,  1901,  and  from 
Franklin  and  Marshall  College,  Lancaster,  Pa.,  with  the  degree 
of  Ph.B.,  in  June,  1904. 

In  October,  1904,  he  entered  Johns  Hopkins  University  as 
a  graduate  student  in  Chemistry,  his  subordinate  subjects 
being  Physical  Chemistry  and  Physics. 

During  the  years  1905-1906  and  1906-1907  he  was  absent 
from  the  University  instructing  in  Chemistry  at  Maryland 
College.  During  1908-1909  he  held  the  position  of  laboratory 
assistant  to  Prof.  Renouf  at  Johns  Hopkins  University. 


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